The rapid infusion of citrate anticoagulant during large volume leukapheresis (LVL) results in acute decreases in serum concentrations of the physiologically active (ionized) form of calcium and magnesium leading to citrate toxicity. Intravenous (IV) Ca is considered to be safe, effective prophylaxis against the toxic symptoms during LVL in healthy donors. In our previous studies we found that when dosed at 0.6 mg Ca ion/mL-ACDA or higher, depending on donor's symptoms, healthy donors experience a 20-40% increase in total Ca (tCa) and 10-20% decrease in ionized Ca (iCa) at the end of apheresis, followed by an asymptomatic 10-15% increase in iCa levels at 30 min, and a return to normal Ca values within 2 hrs. However, IV Ca administration has been reported to cause skin necrosis and symptomatic hypercalcemia, and the use of IV Ca prophylaxis is considered a risk factor for clot formation and/or severe arrhytmia. In addition, the consequences and appropriate management of this procedure in patients with renal dysfunction are not known. In our study of 1, 643 LVL that were performed with IV Ca prophylaxis only two episodes of symptomatic hypercalcemia occurred (iCa=1.53 and 1.75 mmol/L, respectively) both due to equipment malfunction and operator error. In addition, out of four patients with mild to moderate renal dysfunction secondary to lupus nephritis or antibiotic toxicity for CGD who underwent 23 to 32L LVL for autologous PBSC transplantation or gene therapy, two developed symptomatic hypercalcemia (iCa 1.98 mmol/L). In both cases the symptoms occurred shortly after the end of the procedure when citrate is rapidly metabolized resulting in an increase in the concentration of serum iCa. In all cases normalization of iCa was achieved by post-apheresis hydration with normal saline with or without administration of citrate. There were no reports by the donors or patients of skin necrosis or other irritations at the site of the venipuncture.[unreadable] Based on these data adverse effects of IV Ca prophylaxis in healthy donors are very rare and are avoidable. In cases when hypercalcemia develops a reduced dose of Ca, appropriate post-apheresis hydration, and careful laboratory monitoring should be instituted.